Lecture 15
Chemical methods have various modes of action. By understanding the the mechanisms of drugs, one can better understand organisms and how to control them. Most drugs today are combination drugs, which have multiple modes of action to more effectively kill bacteria. The following chemical methods kill bacteria by denaturing their''' protein enzymes'. Protein Coagulation Protein coagulation is a possible result of protein denaturation. Because the 3D structure of the protein is destroyed by breaking hydrogen and disulfide bonds, the solubility of the protein can change, and can even sometimes solidify or precipitate. An observable example of protein coagulation is the frying of an egg. Protein coagulation disrupts the function of enzymes and kills bacteria. Chemicals that are cidal to bacteria through this process are known as '''protoplasmic poisons'. Protoplasm made of proteins, and since all bacteria have a protoplasm, protoplasmic poisons are considered a broad spectrum drug, effective against both Gram-positive and Gram-negative bacteria. Any cell, including human cells have protoplasm. Therefore, protoplasmic poisons are used externally instead of systematically, without entering our blood stream. Ingested drugs that are not absorbed by the gastrointestinal tract are also considered external. Alkalies and Acids Bases and acids are too strong to be used for treatment because they are too damaging for all living organisms and chemicals. These are useful for research or cleaning. Sodium hydroxide (NaOH) can be used for dissolving the shell of a nematode egg. Ammonium hydroxide '''(NH4OH) is used as a disinfectant for floors. '''Benzoic acid can be used as is, but is not very water soluble. Instead, salts like potassium benzoate (Diet Pepsi) or sodium benzoate (Diet Coke) are used in foods as anti-fungals. Propionic Acid is used as calcium propionate in breads, also as an anti-fungal. Phenols Phenols are rated "intermediate" in effectiveness because they are effective in the presence of organic matter like vomit and feces. They are strongly microbiocidal against vegetative cells. Phenols can penetrate the wax coating of a mycobacterium. In addition, phenols are analgesic, or pain-killing. On the other hand, phenols aren't reliably sporocidal, which means they are not good at sterilizing. They are also ineffective against hepatitis B, and are caustic. In regards to the environment, phenols accumulate in nature and are hard to metabolize. Phenol Phenol is a basic phenol ring, and was the first surgical disinfectant, used in the civil war. Joseph Lister would use phenol to disinfect the surgical tables of Staphylococcus aureus. Even today, every disinfectant is compared to phenol in terms of how well it disinfects things, and is given a phenol coefficient. Phenol is still used today as a preservative in some vaccines including the pneumonia vaccine, and as a disinfectant for ear tubes. However, phenol is still highly caustic. Cresols Cresols are methylated phenols in either the ortho, meta, and para positions. Lysol used to use a mixture of the three isomers, also known as tricresol, in their products. Because tricresol is less soluble than phenol, an emulsifying agent is used to keep tricresol suspended. Most of the time, cresols are distilled from coal tar, but can also be synthesized by methylating a phenol. Today, cresols are still used under the brand name Creolin, which has a dark brown/tan color, to clean animal quarters like horse stables. Like most phenols, cresols are hard to break down and stay in the environment. **'o-phenylphenol' O-phynylphenol, or 2-phynylphenol is commonly used in spray disinfectants. McKesson used o-phenyl phenol in addition to 59% alcohol as a detergent for hard surfaces. For this to work, it needs to stay on the surface for 10 minutes at 25°C. 'Salts of (Heavy) Metals' Metal salts are relatively low-activity because they are inactivated by proteins and because an infection can develop beneath the scab that forms. Because it is irritating, these salts may delay healing, and can sometimes even be poisonous. 'Mercuric bichloride' Mercuric bichloride, HgCl2, was used in the past in a 1-2% solution as a disinfectant for seeds. The main problem is that mercury accumulates in the environment and is very polluting. 'Thimerosal (Merthiolate)' Merthiolate was used as an antiseptic until it was taken off the OTC market in 1998. Today, it is used mostly in vaccines as a preservative. Because the mercury inside vaccines was thought to cause autism, they started removing the merthiolate before injection so that there's only trace amounts left. 'Silver Nitrate' Silver nitrate was used to prevent ophtalmia neonatorum, caused by Neisseria gonorrhea and Chlamydia trachomatis. It was effective against gonorrhrea but less effective against chlamydia. It was replaced by Erythromycin as the drug of choice for ophtalmia neonatorum. Silver nitrate is still very commonly used in hospitals to coat catheters (IV or urinary), bedsheets, and furniture. 'Argyrol' Argyrol was a 5-20% colloidal suspension of silver in gelatin. It was used up to the 1940s to prevent gonorrhea by rubbing it on the urethra after intercourse. Argyrol was rendered obsolete by the discovery of penicillin. 'Silver Sulfadiazine' Silfer sulfadiazine is a sulfa drug that is also the gold standard for treating 2nd or 3rd degree burn patients. This combines two modes of action: the protein coagulation of silver and the antimetabolite of sulfadiazine. 'Zinc' Zinc oxide or zinc chloride are anti-fungals that are used as preservatives in certain brands of mouthwash. 'Copper' Copper is an anti-fungal that are sometimes used in socks to get rid of the odor causing microorganisms. Just like silver, it is readily released into its systems, denaturating proteins effectively. 'Alcohols' Generally, alcohols are not very effective as as other disinfectants because they lack residual action and evaporate too quickly. Alcohols increase in effectiveness with their molecular weight, but alcohols that are not water-soluble cannot be used as a disinfectant. 'Methanol' Not effective as a disinfectant and not really used. 'Ethanol' Used as a disinfectant in some rubbing alcohols in a 70% solution. A 70% concentration works to disinfect E. coli but a more diluted concentration (35%) will not. 'Isopropyl Alcohol' Isopropyl alcohol is a pungent disinfectant that is used in some rubbing alcohol in a 70-99% concentration. Unlike ethanol, isopropanol is effective even diluted down to 35%. 'Benzyl Alcohol' Benzyl Alcohol is used as a preservative in''' intravenous solutions''' even though it is not very water soluble. It must not be used with newborns because they lack the proper enzymes to fully break it down. Oxidizing Agents Oxidizing agents denature proteins either by adding oxygen to or removing hydrogen from functional groups in enzymes. Most of these oxidizing agents will remove hydrogen from two sulfhydryl groups to yield a mercaptide group. 'Halogens' Halogens (Cl and I, but not Br) are rated intermediate in effectiveness because they kill bacteria, viruses, fungi, amoeba, and even spores under the best conditions. However, they are inactivated by an alkaline pH or any organic matter. In other words, they bind to organic matter and are used up. They are irritating and slow down healing, and is also volatile, which means that they don't store well. The activity declines upon drying because the halogen is no longer available for disinfecting. 'Iodine Tincture' Iodine tincture is a commonly-used antisceptic. It is usually 2% in a mixture of ethanol and water. 'Iodophors' Iodophors have a solubilizing agent for iodine to help stabilize it in solution. Betadine, for example, uses polyvynil alcohol. Betadine is commonly used to prepare for surgery, and in some countries, is being tested for use on ophtalmia neonatorum. Can be used before inserting a catheter but it must be on site for two minutes. 'Chlorine Gas' Chlorine gas is a toxic gas that is used for water treatment. Chlorine binds to anything colloidal, such as feces, vomit, or bacteria. It is added until there is a residual concentration of .5 to 1 ppm, which is enough to kill all the bacteria and a little more just to be safe. It is effective but has limited use because it is corrosive and toxic. 'Sodium Hypochlorite' In bleach, NaOCl is present in a 5.25% concentration. Bleach is extremely caustic and irritating; it can burn skin, eyes, and irritates the respiratory tract if inhaled (basically everything on the MSDS list). NaOCl is diluted 1/10 of its original concentration from bleach before use, resulting in a .525% concentration in the final solution. This dilution must be made fresh (daily), because Cl evaporates easily and the concentration degrades rapidly over time. This diluted solution is used to disinfect needles from HIV and hepatitis, and clean kidney dialysis machines. 'Hydrogen Peroxide' H2O2 is an ideal antisceptic disinfectant '''at a '''3% concentration because it is not very toxic to humans; our catalase breaks it down into O2 bubbles and H2O. Its mode of action is oxidation, which is a non-specific chemical combination. When broken down by our catalase, the O2 released can kill anaerobic bacteria like tetanus. However, many microorganisms also have catalase and are resistant to the H2O2. However, it is no longer used as a routine disinfectant because it damages our cells and most people are protected against tetanus by the vaccine. Streptococcus pyogenes, which can cause Necrotizing fasciitis, is easily controlled by 2% H2O2 because it lacks catalase. Necrotizing fasciitis deprives tissues of O2 and looks like the flash is being eaten. H2O2 is prefered to antibiotics because there is often poor blood flow to extremities, and H2O2 also acts quickly. At higher concentrations of 10%, hydrogen peroxide can be used as a sterilant for heat labile things such as plastic surgical implants. At this concentration, hydrogen peroxide can no longer be used on human tissue because it is highly caustic. Alkylating agents Functional groups can be denatured by bonding to an organic group. 'Formaldehyde' Formaldehyde gas works by binding to the sulfhydryl group and denaturing the protein. Formaldehyde is commonly used as formalin, which is a formaldehyde solution in water, usually at a 37% concentration. It is diluted to 8% and combined with an alcohol to make a sterilizing solution. This was used as a sterilant for scapels because it didn't dull the blade like heat methods or oxidants. Formaldehyde is still used in embalming solutions and as a sterilant for vaccines that is removed, just like merthiolate. 'Gluteraldehyde' Gluteraldehyde is a lot less toxic and is slowly sporocidal '''even at a low concentration of 2% for 3 hours. It is used to sterilize '''dental offices, respiratory therapy treatment, and cow teats. 'Ethylene Oxide' Ethylene oxide is a simple epoxide gas that can be used to sterilize powders amongst other things. It is a cold sterilant, but it is carcinogenic and explosive. 48 hours to sterilize. Nowadays, it is regulated by OSHA.